Jeffrey A Brinker, M.D.
- Professor of Medicine
- Joint Appointment in Radiology and Radiological Science
This fat distribution is associated with hyperinsulinemia buy serevent american express asthma score definition, impaired glucose tolerance serevent 25 mcg with visa asthma treatment in qatar, diabetes mellitus order serevent canada asthmatic bronchitis dx code, and an increase in androgen production rates 120, 121 and 122 resulting in decreased levels of sex hormone-binding globulin and increased levels of free testosterone and estradiol. The adverse impact of excess weight in adolescence can be explained 125, 126 by the fact that deposition of fat in adolescence is largely central in location. Weight loss in women with lower body obesity is mainly cosmetic, whereas loss of central body weight is more important for general health because an improvement in cardiovascular risk is associated with loss of central body fat. Hyperinsulinemia and hyperandrogenism, however, are not confined to anovulatory women who are overweight. It is important to note that the combination of 42, 127, 128, 129 and 130 increased androgen secretion and insulin resistance has been reported in both obese and nonobese anovulatory women. In our view, these two groups represent the ends of a spectrum, and division of this clinically broad spectrum of patients is artifactual and unhelpful. Hyperinsulinemia and hyperandrogenism are not explained, therefore, solely by obesity, and specifically, android obesity. However, the presence of obesity adds 42, 135, 136 the insulin resistance and hyperinsulinemia associated with obesity to that which is specifically unique to the anovulatory, polycystic ovary state. Large doses of insulin were administered to a 16-year-old female with insulin resistance secondary to 140 insulin receptor autoantibodies; the increased insulin levels increased her circulating testosterone levels. With resolution of her insulin resistance, her testosterone levels returned to normal, indicating that the hyperinsulinemia stimulates and increases testosterone and not vice versa. Indeed, there are 6 reasons to believe that hyperinsulinism causes hyperandrogenism: 141 1. The administration of insulin to women with polycystic ovaries increases circulating androgen levels. The administration of glucose to hyperandrogenic women increases the circulating levels of both insulin and androgens. The experimental reduction of insulin levels in women reduces androgen levels in women with polycystic ovaries, but not in normal women. However, the effect is not great, and may be limited to lean patients with mild hyperinsulinemia. Because the increase in insulin is not always extreme, it has been proposed that insulin activates a signaling system separate from glucose transport, specifically, that 152 insulin operates via inositolphosphoglycan to stimulate steroidogenesis. There are two other important actions of insulin which contribute to hyperandrogenism in the presence of hyperinsulinemia: inhibition of hepatic synthesis of sex hormone-binding globulin and inhibition of hepatic production of insulin-like growth factor binding protein-1. It is likely that these characteristics of polycystic ovaries are secondary to increased anovulation, hyperinsulinemia, and increased androgens, rather than indicating a primary, etiologic role. The answer to this question is 163 not known, but a logical speculation is that an ovarian genetic susceptibility is required, although it may be that the existence of long-term anovulation must be present and even precede hyperinsulinemia. Diazoxide and octreotide, the long-acting analogue of somatostatin, both inhibit insulin 146, 164 secretion, but are accompanied by worsening glucose intolerance. The best approach is to improve peripheral insulin sensitivity, thus achieving reductions in insulin secretion and stability of glucose tolerance. Metformin and troglitazone, oral agents used to treat diabetes mellitus, have been administered to anovulatory women with polycystic ovaries. Metformin improves insulin sensitivity, but the primary effect is a significant reduction in gluconeogenesis, thus decreasing hepatic glucose production. In a group of obese women with polycystic 170 ovaries, 90% of the women treated with metformin and 50 mg clomiphene ovulated compared with 8% in the group treated with placebo and clomiphene. However, 171 there has been controversy, suggesting that the improvement was the result of the weight loss that often accompanies the use of metformin. In a study designed to 172 control the effect of body weight, the administration of metformin was without effect on insulin resistance in extremely overweight women with polycystic ovaries. In another well-designed study, metformin again had no effect on insulin resistance when body weights remained unchanged, and in this study baseline weights and 173 hyperinsulinemia were only modestly increased. In lean, anovulatory women with hyperinsulinemia, metformin treatment reduced hyperandrogenemia although 174 there was no change in body weight; however, a decrease in the waist to hip ratio accompanied a reduction in the hyperinsulinemia. This study indicates that both obese and nonobese patients with hyperinsulinemia respond to metformin treatment. Perhaps only certain patients will respond to metformin, and, thus, patient selection could influence the reported results. The thiazolidinediones markedly improve insulin sensitivity and insulin secretion (improved peripheral glucose utilization and b-cell function) without weight changes. There is little doubt that these drugs can produce significant and beneficial improvements in this condition, although metformin may be effective only when weight loss occurs. However, is short-term use better than our standard methods of the induction of ovulation, and are these drugs safe during pregnancy and lactation? Is long-term use for preventive health care cost-effective and compatible with good drug compliance? How effective are these agents in women who are of normal or only slightly elevated body weight? Are there any unwanted effects associated with long-term use (liver enzyme changes have occurred in rare patients with troglitazone)? It is our prediction that during the clinical lifetime of this text, metformin and troglitazone (and perhaps new related drugs) will be increasingly used for anovulatory women resistant to clomiphene treatment and to prevent the cardiovascular and metabolic consequences of hyperinsulinemia. The Clinical Consequences of Persistent Anovulation Anovulation is the key feature of this condition and presents as amenorrhea in approximately 50% of cases and with irregular, heavy bleeding (dysfunctional uterine 12, 177 bleeding) in 30%. True virilization is rare, but 70% of anovulatory patients complain of cosmetically disturbing hirsutism.
Grade B buy serevent 25 mcg with mastercard asthma kids natural remedies, Level 2++ C Men should be warned that excessive alcohol intake is detrimental to semen quality buy serevent 25 mcg without a prescription asthma treatment 3 year old. Overall generic serevent 25mcg line asthma 504 plan, moderate caffeine consumption (one to two cups of coffee per day or its equivalent) before or during pregnancy has no apparent adverse effects on fertility or pregnancy outcomes. The effect of smoking on male infertility is less certain, though there is an association with reduced semen parameters. Grade B, Level 1+ 23 D Men who smoke should be informed that smoking is associated with reduced sperm parameters. Nevertheless, such drug use generally should be discouraged for both men and women because they have well-documented harmful effects on the developing fetus. A specifc enquiry should be made to couples concerned about their fertility and appropriate advice should be offered. Women exposed to toxins and solvents such as those used in the dry cleaning and printing industries. B Couples seeking treatment for infertility should be routinely screened for usage of long term prescription medication, as some have been known to affect fertility. Grade B, Level 2++ C Couples seeking treatment for infertility should also be routinely screened for occupational hazards and given appropriate advice. Some advocate zinc, selenium, and vitamin E supplements for men with abnormal semen parameters of unknown cause, although the evidence for effcacy is weak. For women who have previously had an infant with a neural tube defect or who are receiving anti-epileptic medication, a higher dose of 5 mg per day is recommended. Cervical screening should be offered in accordance with the national cervical screening programme guidance. Grade B, Level 2+ B If the frst sperm analysis result is abnormal, the patient should be offered a repeat test from the same laboratory at least 3 months after the initial analysis. Women with regular monthly menstrual cycles should be informed that they are likely to be ovulating. D Use of basal body temperature charts and home ovulation kits alone to predict ovulation should not be recommended to patients with fertility problems as these are not always reliable in predicting ovulation and leads to unnecessary anxiety and stress for the patient. If cycles are irregular or prolonged, this test may need to be repeated again weekly thereafter until the next menstrual period. Patients with high levels of gonadotrophins should be informed that they are likely to have reduced fertility. This can identify women at high risk of having tubal damage as a cause of their infertility. Grade A, Level 1+ Chlamydia infection is a common sexually transmitted disease which results in tubal disease. Untreated infection may 30 lead to pelvic infammatory disease which can cause scarring of the fallopian tube and therefore tubal infertility. B Laparoscopy and dye hydrotubation should be offered for women with comorbidities, such as pelvic infammatory disease, previous ectopic pregnancy or endometriosis. It is more appropriate for women who are thought to have comorbidities such as pelvic infammatory disease, previous ectopic pregnancy or endometriosis. Laparoscopy allows proper assessment of tubal and pelvic pathology and possibility of corrective surgery at the same setting. C Fertiloscopy and transvaginal hydrolaparoscopy should not be offered routinely as an alternative to laparoscopy hydrotubation as their diagnostic accuracy still require further evaluation. It may be used to evaluate posterior uterus, pelvic sidewall, adnexal and to identify tubal pathology. Being a relatively new procedure its diagnostic accuracy requires further evaluation. These lesions may compromise implantation and pregnancy rates in spontaneous and treatment cycles. Therefore, uterine cavity assessment has been suggested as a routine investigation in subfertile women. Grade C, Level 2+ Transvaginal ultrasound is well tolerated by patients and has a high positive predictive value (85-95%). However, it should not be offered as an initial investigation due to its invasiveness and availability of other modalities with comparable sensitivity. Hysterosalpingography and saline infusion sonohysterogaphy are other alternatives which are highly sensitive and specifc in identifying intrauterine abnormalities. Saline infusion sonohysterogaphy, by instilling sterile saline into uterine cavity, has a high sensitivity in detecting polyps, submucousal fbroid and synechiae. Functional hypothalamic pituitary failure - this group of patients suffers from exercise-associated, nutritional or pyschogenic stresses, leading to a failure of hypothalamic function. C For patients with functional hypothalamic pituitary failure who desire fertility, ovulation induction therapies may be indicated. However, the achievement of a healthy weight and modifcation of lifestyle should be tried frst. Grade C, Level 2+ Behavioural modifcation and achievement of adequate caloric intake is not only simple but highly effective. Moreover, inadequate caloric intake is likely to be inadequate for normal fetal development, resulting in higher rates of miscarriages. This is especially important as weight gain has been shown to have a greater effect on bone mineral densities than hormone replacement therapy in the form of the combined oral contraceptive pill. If the medication which causes anovulation cannot be altered or discontinued, referral to a reproductive medicine specialist for further management is indicated. Interdisciplinary management is hinged upon supportive, non-specifc interventions,63 with about half of patients achieving adequate weight gain and resumption of their menstrual cycle. Polycystic ovaries by doing a pelvic ultrasound scan to determine features in accordance with the Rotterdam criteria (either 12 or more follicles measuring 2-9 mm in diameter, or an ovarian volume of > 10 cm3) 2. Grade D, Level 4 Management of polycystic ovary syndrome Effective treatment of patients with polycystic ovary syndrome requires that the specifc goal(s) of therapy be frst established.
Host variables are stratiﬁed with regard to physiologic capacity to with- stand infection buy discount serevent 25mcg on-line asthma definition xenophobe, treatment order serevent in india asthma treatment trials, and disease morbidity order online serevent asthma treatment europe. The B-host has a local (B ), a systemic (B ), or a com- L/S bined local and systemic (B ) compromise. Treatment of C-hosts may potentially result in greater patient morbidity following treatment than it would before intervention. Surgical treatment of osteomyelitis involves three main facets: (1) exten- sive debridement, (2) vascular soft tissue coverage, and (3) bone stabiliza- tion. An aggressive debridement is crucial to achieving successful eradication of osteomyelitis. All nonviable tissue must be removed to prevent residual bacteria from persistently reinfecting the bone. In addi- tion, a high-speed burr should be used to debride the cortical bone edges 98 S. Multiple cultures of all debrided material should be obtained before the initiation of antibiotic therapy. The patient may require several debridements until the wound is considered to be clean enough to accept soft tissue coverage. Soft tissue reconstitution may involve a simple skin graft, but it often requires a local transposition of muscular tissue or vascularized free tissue transfers to effectively cover the debrided bone segment. These muscle ﬂaps provide a fresh bed of vascularized tissue to assist in bone healing and antibiotic delivery. Finally, bone stability must be achieved with bone grafting being undertaken when necessary to bridge osseous gaps. Cancellous and cortical autografts are commonly used, with vascularized bone transfer (vascularized free ﬁbular, iliac, and rib grafts) being occasionally necessary. Although technically demanding, vascularized bone grafts provide a fresh source of blood ﬂow into previously devascularized areas of bone. The recent advent of bone distraction has been used in lieu of bone grafting or complex soft tissue procedures. Altough technically demand- ing, application of a small pin (Ilizarov) or half-pin external ﬁxator with bone distraction following a cortical osteotomy can produce columns of bone that ﬁll segmental defects. As distraction is carried out, the soft tissues regenerate along with the bone to cover the newly generated tissue. Recent results seem encouraging, as these patients appear to achieve greater success rates for limb-sparing methods as compared to patients undergoing more conventional bone replacement techniques. Septic Arthritis As with children, septic arthritis in adults can develop from hematogenous sources, direct inoculation, contiguous soft tissue infection, or periarticu- lar osteomyelitis. Several factors happen implicating and predisposing patients to septic arthritis, with systemic corticosteroid use, preexisting arthritis, and joint aspiration being the three most common factors reported. As with children, Staphylococcus aureus is the most common pathogen isolated from infected adult joints (44%). Neisseria gonorrhoeae is another common adult pathogen, with a reported incidence of 11%. The joints most commonly involved are the knee (40%–50%), hip (20%–25%), and shoulder and ankle (10%–15%). Adult patients present in a manner similar to children in that pain, swell- ing, and a decreased range of motion are frequent complaints. Treatment of an adult with a septic arthritis requires aggressive irriga- tion and debridement utilizing either arthroscopic techniques or an open arthrotomy. Antibiotics are often delivered initially via parenteral routes, with patients being switched to oral therapy when demonstrating clinical improvement in conjunction with maintaining high bactericidal titers of at least 1 : 8. Open Fractures By deﬁnition, an open fracture involves exposure of fractured bone to the extracorporeal environment, thus increasing the risk of bone contamina- tion from foreign debris and bacteria. In addition, open fractures are often associated with severe soft tissue damage, devascularization, and devital- ization of bone fragments, further increasing the susceptibility of the bone to infection. Open fractures are often graded on the degree of fracture comminution and the degree of soft tissue disruption. Although not uni- versally accepted, the Gustilo–Anderson classiﬁcation is widely used because of its ease of application and prognostic ability. With rare exceptions, patients should be taken to the operating room within 6 hours of injury. Wounds should not be explored in the emergency room as further soft tissue damage may be incurred. Active bleeding can almost always be controlled with local compression before surgical exploration. Cultures taken in the emer- gency room setting or in the operating room before debridement have proven to be of little value in dictating treatment. Cultures are, therefore, taken at the index surgical procedure only in rare instances. Wounds should be assessed, gently irrigated with sterile saline, and dressed with a sterile dressing in the emergency department. Reduction of severely con- taminated fractures should be avoided in the emergency room to prevent the drawing of foreign debris into the wound. If the fracture is grossly contaminated, such as in a barnyard injury, then a penicillin is added to this regimen. Assessment of the extent of injury and aggressive debridement should be undertaken in the operating room in an emergent manner.
- Medicines to treat for the liver disease, including ascites
- Kidney failure
- It can take up to 2 years to recover speech. Not everyone will fully recover.
- Mental changes or confusion
- Receiving many intramuscular injections
- Baked potato
Preterm delivery (occurring in up to 19% of cases) cheap 25mcg serevent amex asthma definition volume, occurs more frequently when the foetus is affected buy serevent online from canada asthma symptoms wont go away, owing to increased fragility of the 42 membranes order generic serevent line asthmatic bronchitis symptoms in adults. Whether the nature of aortic root dilatation is progressive is also a matter of debate. Overall complications were rare in childhood but 25% of patients had a first complication by the age of 20 years and more than 80% had suffered from at least one complication by the age of 40 years. The median survival was 48 year meaning that 50% of patients had died before that age. Arterial and organ rupture are associated with a higher mortality rate than intestinal rupture (estimated only 2%), which was more often amenable to surgical treatment. Also, the nature of the first complication does not seem to predict the nature of the next complication. A more recent smaller scale study on 31 patients treated for vascular events showed slightly better survival rates with 68% 26 of patients surviving at the age of 50 years. As both of these reported surveys were retrospective, caution in the interpretation is warranted. Prospective large scale studies are essential for the correct interpretation of survival rates. The latter approach, although generally efficient, can miss whole exon, multiple exon or whole gene deletions. More recently, next generation sequencing is evolving as the new sequencing methodology. Such errors distort the dimensions of the triple helix, such that helical winding and therefore incorporation of mutant alpha chains into mature triple helices, is impaired. This leads to diminished collagen secretion and assembly, such that tissues which contain the mutant molecules become seriously weakened. Similar effects arise from exon skips in which shortened triple helices are similarly disruptive. In the case of stop codon mutations or large deletions, dosage effects are exerted, by virtual haplo-insufficiency. Within the glycine substituting group, substitutions for serine and arginine seem to have a better outcome than 52 those for valine and aspartic acid. These patients can present with vascular ruptures, but show no distinguishable histological features. Very obvious cases can be distinguished by the presence of early onset severe periodontal disease leading to early teeth loss and the typical appearance of chronically inflamed pretibial plaques. In families with more subtle periodontal fragility, formal testing is necessary to distinguish them. Other systemic findings include craniosynostosis, joint hypermobility, bicuspid aortic valve, blue sclerae. These patients also present with widespread vascular involvement (aneurysms throughout the arterial tree) and thin, velvety skin. Other important features include long bone overgrowth (dolichostenomelia, pectus deformities and arachnodactyly). The diagnosis of Marfan syndrome is based on the 64 identification of typical clinical manifestations as defined in the revised Ghent nosology. Arterial dissection in Marfan syndrome is confined to the aorta and is nearly always preceded by aortic dilatation. The risk of aortic rupture 65 or dissection is not only influenced by the degree of aortic dilation. Arterial stenoses may occur in the systemic as well as in the pulmonic vascular bed and mild aortic root dilatation has occasionally been reported. So far, 69,70 no vascular ruptures have been reported in patients with this syndrome. Clinical presentation is extremely variable with regards to the age of onset and degree of progression of the dilation. Most commonly medial hyperplasia leads to a classic “strings of beads” stenotic arterial appearance. Thus whilst jogging is acceptable, sprinting is contraindicated and similar considerations apply to tennis as contrasted with squash rackets. Similarly, because of the adverse effects of vascular overload, regular monitoring of blood pressure and meticulous control to normal values is sensible in both young and older adults. Because of significant risks of arterial pathology and fragility, any sudden onset of unusual pain needs prompt and meticulous investigation, by both clinical examination and appropriate non-invasive imaging. Anti-platelets and anticoagulants should be used only after careful consideration of the risks and benefits. When at home affected patients should identify a specific medical attendant, such as a general practitioner, paediatrician, adult physician or clinical geneticist, who can co-ordinate information for emergency treatment, if 76 required. These include cross-matching of adequate amounts of blood for transfusion, avoid intramuscular premedication, establish adequate peripheral venous access and the avoidance of arterial lines and central venous lines whenever possible. If surgery is unavoidable, minimal and very gentle vessel manipulation is essential and anastomoses should be strengthened with Teflon pledgets (non-absorbable 88 Chapter 6 26 fabrics that act as bolsters when placed on a suture) and carried out without tension. Surgery is more likely to be successful if the surgeon is well-informed about the condition. The types of technical difficulties in vascular emergencies have been well illustrated by Ascione et al. Ideally and wherever practicable the management and imaging of such complex and potentially lethal problems should be centralized in designated specialist vascular centres.
25mcg serevent with amex. Differences of Asthma and COPD.
History the location of the pain is the major point to obtain from the patient history purchase 25 mcg serevent overnight delivery asthma young living essential oils. The majority of patients complain of localized symptoms in the neck cheap serevent 25mcg without a prescription asthma educator definition, with and without referral of pain between the scapulae or shoulders purchase 25mcg serevent amex asthma treatment medscape. The pain is described as vague, diffuse, axial, nondermatomal, and poorly localized. The pathogenesis of this type of complaint is attributed to struc- tures innervated by the sinuvertebral nerve or the nerves innervating the paravertebral soft tissues and is generally a localized injury. The Spine 277 Another group of patients complains of neck pain with the addition of arm involvement. The degree of nerve root involvement can vary from a monoradiculopathy to multiple levels of involvement. It is described as a deep aching, burning, or shooting arm pain, often with associated paresthesias. The pathogenesis of radicular pain can derive from soft tissue (herniated disk), bone (spondylosis), or a combination of these two. Finally, a third group of patients complains of symptoms secondary to cervical myelopathy, which is compression of the spinal cord and usually secondary to degenerative changes. The onset of symptoms usually begins after 50 years of age, and males are more often affected. The natural history is that of initial neurologic deterioration followed by a plateau period lasting several months. The resulting clinical picture is often one of an incomplete spinal lesion with a patchy distribution of deﬁcits. Disability varies with the number of verte- brae involved and with the degree of changes at each level. Common presenting symptoms of cervical myelopathy include numbness and paresthesias in the hands, clumsiness of the ﬁngers, weakness (greatest in the lower extremities), and gait disturbances. Abnormalities of micturi- tion are seen in about one-third of cases and indicate more severe cord involvement. Symptoms of radiculopathy can coexist with myelopathy and confuse the clinical picture. Spinothalamic tract (pain and temperature) deﬁcits may be seen in the upper extremities, the thorax, or the lumbar region and may be in a stocking or glove distribution. Posterior column deﬁcits (vibration and proprioception) are more commonly seen in the feet than in the hands. Usually there is no gross sensory impairment, but a diminished sense of appreciation of light touch and pinprick. A characteristic broad-based, shufﬂing gait may be seen, signaling the onset of functionally signiﬁcant deterioration. Physical Examination the physical examination should begin with observation of the cervical spine and upper torso unencumbered by clothing. One set can be categorized as nonspeciﬁc and found in most patients with neck pain but will not help to localize the type or level of the pathologic process. It can be secondary to pain or, structurally, to distorted bony or soft tissue elements in the cervical spine. Hyperexten- sion and excessive lateral rotation, however, usually cause pain, even in a normal individual. The second type of tender- ness is more speciﬁc and may help localize the level of the pathology. It can be localized by palpation over each intervertebral foramen and spinous process. The next goal of the physical examination is to isolate the level or levels in the cervical spine responsible for the symptomatology. The exam is also important to rule out other sources of pain, which include compression neuropathies, thoracic outlet syndrome, and chest or shoulder pathology. The major focus of the exam is directed at ﬁnding a neurologic deﬁcit (Table 7-1). A motor deﬁcit (most commonly weak triceps, biceps, or deltoid) or diminished deep tendon reﬂex is the most likely objective Table 7-1. Although less reproducible, manual tests and maneuvers that increase or decrease radicular symptoms may be helpful. In the neck compression test, the patient’s head is ﬂexed laterally, slightly rotated toward the symptomatic side, and then compressed to elicit reproduction or aggravation of the radicular symptoms. The axial manual traction test is performed in the presence of radicular symptoms in the supine position. With 20 to 25lb axial traction, a positive test is the decrease or disappearance of radicular symptoms. All these tests are highly speciﬁc (low false-positive rate) for the diagnosis of root compression, but the sensitivity (false-negative rate) is less than 50%. Pyramidal tract weakness and atrophy are more commonly seen in the lower extremi- ties and are the most common abnormal signs. Weakness and wasting of the upper extremities and hands may also be due to combined spondylotic myelopathy and radiculopathy. A diminished or absent upper-extremity deep tendon reﬂex can indicate compressive radic- ulopathy superimposed on spondylotic myelopathy. Sensory deﬁcits in spinothalamic (pain and temperature) and posterior column (vibration and proprioception) function should be documented. Usually there is no gross impairment of sensation; rather, a patchy decrease in light touch and pinprick is seen. Hyperreﬂexia, clonus, and positive Babinski’s signs are seen in the lower extremities. Diagnostic Studies In evaluating any pathologic process, one usually has a choice of several diagnostic tests.